Mitochondrial sodium/calcium exchanger NCLX regulates glycolysis in astrocytes, impacting on cognitive performance

Autor(es)

Cabral-Costa, Joao Victor ; Vicente-Gutierrez, Carlos ; Agulla, Jesus ; Lapresa, Rebeca ; Elrod, John W. ; Almeida, Angeles ; Bolanos, Juan P. ; Kowaltowski, Alicia J.

• Tipo de documento: Artigo Científico
• Fonte: Journal of Neurochemistry; v. N/A, p. 15-pg., 2023-01-09.

Resumo

Intracellular Ca2+ concentrations are strictly controlled by plasma membrane transporters, the endoplasmic reticulum, and mitochondria, in which Ca2+ uptake is mediated by the mitochondrial calcium uniporter complex (MCUc), while efflux occurs mainly through the mitochondrial Na+/Ca2+ exchanger (NCLX). RNAseq database repository searches led us to identify the Nclx transcript as highly enriched in astrocytes when compared with neurons. To assess the role of NCLX in mouse primary culture astrocytes, we inhibited its function both pharmacologically or genetically. This resulted in re-shaping of cytosolic Ca2+ signaling and a metabolic shift that increased glycolytic flux and lactate secretion in a Ca2+-dependent manner. Interestingly, in vivo genetic deletion of NCLX in hippocampal astrocytes improved cognitive performance in behavioral tasks, whereas hippocampal neuron-specific deletion of NCLX impaired cognitive performance. These results unveil a role for NCLX as a novel modulator of astrocytic glucose metabolism, impacting on cognition. (AU)

• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 17/14713-0 - Ca2+ Mitocondrial no Sistema Nervoso Central e Regulação do Metabolismo Energético
• Beneficiário: João Victor Cabral Costa
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 20/06970-5 - Transportadores iônicos mitocondriais como sensores e reguladores do metabolismo energético
• Beneficiário: Alicia Juliana Kowaltowski
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/22178-2 - NCLX na função de astrócitos: metabolismo e homeostase neuronal
• Beneficiário: João Victor Cabral Costa
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado